bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-translational assembly of mammalian nuclear multisubunit complexes
Authors: Kamenova Ivanka , Mukherjee Pooja , Conic Sascha , Mueller Florian , El-Saafin Farrah , Bardot Paul , Garnier Jean-Marie , Dembele Doulaye , Capponi Simona , Timmers H. T. Marc , Vincent Stéphane D. , Tora László 
Published: April 2019

AbstractCells dedicate significant energy to build proteins often organized in multiprotein assemblies with tightly regulated stoichiometries. As genes encoding subunits assembling in a multisubunit complex are dispersed in the genome of eukaryotes, it is unclear how these protein complexes assemble. Here, we show that mammalian nuclear transcription complexes (TFIID, TREX-2 and SAGA) composed of a large number of subunits, but lacking precise architectural details are built co-translationally. We demonstrate that dimerization domains and their positions in the interacting subunits determine the co-translational assembly pathway (simultaneous or sequential). The lack of co-translational interaction can lead to degradation of the partner protein. Thus, protein synthesis and complex assembly are linked in building mammalian multisubunit complexes, suggesting that co-translational assembly is a general principle in mammalian cells to avoid non-specific interactions and protein aggregation. These findings will also advance structural biology by defining endogenous co-translational building blocks in the architecture of multisubunit complexes.
Structural basis of specific H2A K13/K15 ubiquitination by RNF168
Authors: Horn Velten , Uckelmann Michael , Zhang Heyi , Eerland Jelmer , Aarsman Ivette , le Paige Ulric B. , Davidovich Chen , Sixma Titia K. , van Ingen Hugo 
Published: April 2019

AbstractUbiquitination of chromatin by modification of histone H2A is a critical step in both regulation of DNA repair and regulation of cell fate. These very different outcomes depend on the selective modification of distinct lysine residues in H2A, each by a specific E3 ligase. While polycomb PRC1 complexes modify K119, resulting in gene silencing, the E3 ligase RNF168 modifies K13/15, which is a key event in the response to DNA double-strand breaks. The molecular origin of ubiquitination site specificity by these related E3 enzymes is one of the open questions in the field. Using a combination of NMR spectroscopy, crosslinking mass-spectrometry, mutagenesis and data-driven modelling, here we show that RNF168 binds the acidic patch on the nucleosome surface, directing the E2 to the target lysine. The structural model highlights the role of E3 and nucleosome in promoting ubiquitination and provides a basis for understanding and engineering of chromatin ubiquitination specificity.
Single platinum atoms embedded in nanoporous cobalt selenide as electrocatalyst for accelerating hydrogen evolution reaction
Authors: Jiang Kang , Liu Boyang , Luo Min , Ning Shoucong , Peng Ming , Zhao Yang , Lu Ying-Rui , Chan Ting-Shan , de Groot Frank M. F. , Tan Yongwen 
Published: April 2019

AbstractDesigning efficient electrocatalysts for hydrogen evolution reaction is significant for renewable and sustainable energy conversion. Here, we report single-atom platinum decorated nanoporous Co0.85Se (Pt/np-Co0.85Se) as efficient electrocatalysts for hydrogen evolution. The achieved Pt/np-Co0.85Se shows high catalytic performance with a near-zero onset overpotential, a low Tafel slope of 35 mV dec−1, and a high turnover frequency of 3.93 s−1 at −100 mV in neutral media, outperforming commercial Pt/C catalyst and other reported transition-metal-based compounds. Operando X-ray absorption spectroscopy studies combined with density functional theory calculations indicate that single-atom platinum in Pt/np-Co0.85Se not only can optimize surface states of Co0.85Se active centers under realistic working conditions, but also can significantly reduce energy barriers of water dissociation and improve adsorption/desorption behavior of hydrogen, which synergistically promote thermodynamics and kinetics. This work opens up further opportunities for local electronic structures tuning of electrocatalysts to effectively manipulate its catalytic properties by an atomic-level engineering strategy.
Nickel-catalysed selective migratory hydrothiolation of alkenes and alkynes with thiols
Authors: Zhang Yulong , Xu Xianfeng , Zhu Shaolin 
Published: April 2019

AbstractDirect (utilize easily available and abundant precursors) and selective (both chemo- and regio-) aliphatic C–H functionalization is an attractive mean with which to streamline chemical synthesis. With many possible sites of reaction, traditional methods often need an adjacent polar directing group nearby to achieve high regio- and chemoselectivity and are often restricted to a single site of functionalization. Here we report a remote aliphatic C–H thiolation process with predictable and switchable regioselectivity through NiH-catalysed migratory hydrothiolation of two feedstock chemicals (alkenes/alkynes and thiols). This mild reaction avoids the preparation of electrophilic thiolation reagents and is highly selective to thiols over other nucleophilic groups, such as alcohols, acids, amines, and amides. Mechanistic studies show that the reaction occurs through the formation of an RS-Bpin intermediate, and THF as the solvent plays an important role in the regeneration of NiH species.
Partially methylated domains are hypervariable in breast cancer and fuel widespread CpG island hypermethylation
Authors: Brinkman Arie B. , Nik-Zainal Serena , Simmer Femke , Rodríguez-González F. Germán , Smid Marcel , Alexandrov Ludmil B. , Butler Adam , Martin Sancha , Davies Helen , Glodzik Dominik , Zou Xueqing , Ramakrishna Manasa , Staaf Johan , Ringnér Markus , Sieuwerts Anieta , Ferrari Anthony , Morganella Sandro , Fleischer Thomas , Kristensen Vessela , Gut Marta , van de Vijver Marc J. , Børresen-Dale Anne-Lise , Richardson Andrea L. , Thomas Gilles , Gut Ivo G. , Martens John W. M. , Foekens John A. , Stratton Michael R. , Stunnenberg Hendrik G. 
Published: April 2019

AbstractGlobal loss of DNA methylation and CpG island (CGI) hypermethylation are key epigenomic aberrations in cancer. Global loss manifests itself in partially methylated domains (PMDs) which extend up to megabases. However, the distribution of PMDs within and between tumor types, and their effects on key functional genomic elements including CGIs are poorly defined. We comprehensively show that loss of methylation in PMDs occurs in a large fraction of the genome and represents the prime source of DNA methylation variation. PMDs are hypervariable in methylation level, size and distribution, and display elevated mutation rates. They impose intermediate DNA methylation levels incognizant of functional genomic elements including CGIs, underpinning a CGI methylator phenotype (CIMP). Repression effects on tumor suppressor genes are negligible as they are generally excluded from PMDs. The genomic distribution of PMDs reports tissue-of-origin and may represent tissue-specific silent regions which tolerate instability at the epigenetic, transcriptomic and genetic level.
Rabies-based vaccine induces potent immune responses against Nipah virus
Authors: Keshwara Rohan , Shiels Thomas , Postnikova Elena , Kurup Drishya , Wirblich Christoph , Johnson Reed F. , Schnell Matthias J. 
Published: April 2019

AbstractNipah Virus (NiV) is a re-emerging zoonotic pathogen in the genus Henipavirus of the Paramyxoviridae family of viruses. NiV is endemic to Bangladesh and Malaysia and is highly fatal to both livestock and humans (human case fatality rate = 74.5%). Currently, there is no approved vaccine against NiV on the market. The goal of this study was to use a recombinant RABV vector expressing NiV glycoprotein (NiV G) to develop a bivalent candidate vaccine against NiV disease and rabies virus (RABV) disease, which is also a significant health burden in the regions where NiV is endemic. The rabies vector is a well-established vaccine strain that lacks neurovirulence and can stably expresses foreign antigens that are immunogenic in various animal models. Mice inoculated intranasally with the live recombinant RABV/NiV vaccine (NIPARAB) showed no signs of disease. To test the immunogenicity of the vaccine candidate, groups of C57BL/6 mice were immunized intramuscularly with a single dose of live vaccine particles or two doses of chemically inactivated viral particles. Both vaccination groups showed NiV G-specific seroconversion, and the inactivated (INAC) vaccine group yielded higher titers of NiV G-specific antibodies. Furthermore, cross-reactivity of NiV G-specific immune sera against Hendra virus (HeV), was confirmed by immunofluorescence (IF) and indirect ELISA against soluble recombinant HeV glycoprotein (HeV G). Both live and killed vaccines induced neutralizing antibodies. These results indicate that NIPARAB may be used as a killed virus vaccine to protect humans against NiV and RABV, and possibly as a preventative measure against HeV as well.
Statistically downscaled climate dataset for East Africa
Authors: Gebrechorkos Solomon H. , Hülsmann Stephan , Bernhofer Christian 
Published: April 2019

AbstractFor many regions of the world, current climate change projections are only available at coarser spatial resolution from Global Climate Models (GCMs) that cannot directly be used in impact assessment and adaptation studies at regional and local scale. Impact assessment studies require high-resolution climate data to drive impact assessment models. To overcome this data challenge, we produced a station based climate projection (precipitation and maximum and minimum temperature) for Ethiopia, Kenya, and Tanzania using observed daily data from 211 stations obtained from the National Meteorological Agency of Ethiopia and international databases. Moreover, 26 large-scale climate variables derived from the National Centers for Environmental Prediction reanalysis data (1961–2005) and second generation Canadian Earth System Model (CanESM2, 1961–2100) are used. Statistical Down-Scaling Model (SDSM) is used to produce the required high-resolution climate projection by developing a statistical relationship between the large- and local-scale climate variables. The predictors are analysed more than 16458 times and we provided 20 ensembles for the current (1961–2005) and future (2006–2100, under RCP2.6, RCP4.5, and RCP8.5) climate.
Automated cell-based luminescence assay for profiling antiviral compound activity against enteroviruses
Authors: Zhang Mingyu , Zhang Yong , Wang Yan , Lv Wanyu , Zhang Yanyang 
Published: April 2019

AbstractWe describe the development, optimisation, and validation of an automated, cell-based and high-throughput screening assay using existing luminescence-based ATPlite reagents for identifying antiviral compounds that inhibit enterovirus replication. Antiviral efficacy was determined by measuring the ATP levels in cells that were protected from the viral cytopathic effect (CPE) by the antiviral compounds pleconaril and rupintrivir. CPE-based assay conditions were optimised at a cell density of 5000 cells/well and a viral infection dose of 100 CCID50 in 384-well plates. The assay exhibited excellent robustness, with Z′-factor values between 0.75 and 0.82, coefficients of variation between 0.33% and 1.45%, and signal-to-background ratios ranging from 6.92 to 22.6 when testing three enterovirus A71 isolates circulating in China. The assay was also suitable for screening other picornaviruses, such as poliovirus, coxsackievirus, echovirus, and parechovirus.
Transcriptome Profiles of Alternaria oxytropis Provides Insights into Swainsonine Biosynthesis
Authors: Li Xin , Lu Ping 
Published: April 2019

AbstractSwainsonine (SW) is a toxic alkaloid biosynthesized by the endophytic fungus Alternaria oxytropis in Oxytropis glabra. The biosynthetic pathway of SW is poorly understood. Saccharopine reductase/dehydrogenase of fungus plays an important role in this pathway. The gene knocked out mutant M1 in A. oxytropis was constructed in our previous work. In this study, the transcriptome of wild-strain OW7.8 and M1 was firstly sequenced to understand the biosynthetic pathway and molecular mechanism of SW in A. oxytropis. A total of 45,634 Unigenes were annotated. 5 genes were up-regulated and 11,213 genes were down-regulated. 41 Unigenes possibly related to the biosynthesis of SW were identified by data analyzing. The biosynthesis pathway of SW in the fungus was speculated, including two branches of P6C and P2C. Delta1-piperidine-2-carboxylate reductase, lysine 6-dehydrogenase, and saccharopine oxidase/L-pipecolate oxidase were involved in P6C. 1-piperidine-2-carboxylate/1-pyrroline-2- carboxylate reductase [NAD(P)H] and delta1-piperidine-2-carboxylate reductase were involved in P2C. Saccharopine reductase was involved in both. In addition, 1-indolizidineone was considered to be the direct precursor in the synthesis of SW, and the hydroxymethylglutaryl-CoA lyase catalyzed the synthesis of SW. Here we analyzed details of the metabolic pathway of A. oxytropis SW, which is of great significance for the follow-up research.
A novel approach to differentiate rat embryonic stem cells in vitro reveals a role for RNF12 in activation of X chromosome inactivation
Authors: Magaraki Aristea , Loda Agnese , Gontan Cristina , Merzouk Sarra , Sleddens-Linkels Esther , Meek Stephen , Baarends Willy M. , Burdon Tom , Gribnau Joost 
Published: April 2019

AbstractX chromosome inactivation (XCI) is a mammalian specific, developmentally regulated process relying on several mechanisms including antisense transcription, non-coding RNA-mediated silencing, and recruitment of chromatin remodeling complexes. In vitro modeling of XCI, through differentiation of embryonic stem cells (ESCs), provides a powerful tool to study the dynamics of XCI, overcoming the need for embryos, and facilitating genetic modification of key regulatory players. However, to date, robust initiation of XCI in vitro has been mostly limited to mouse pluripotent stem cells. Here, we adapted existing protocols to establish a novel monolayer differentiation protocol for rat ESCs to study XCI. We show that differentiating rat ESCs properly downregulate pluripotency factor genes, and present female specific Xist RNA accumulation and silencing of X-linked genes. We also demonstrate that RNF12 seems to be an important player in regulation of initiation of XCI in rat, acting as an Xist activator. Our work provides the basis to investigate the mechanisms directing the XCI process in a model organism different from the mouse.
Controlling frequency dispersion in electromagnetic invisibility cloaks
Authors: Klotz Geoffroy , Malléjac Nicolas , Guenneau Sebastien , Enoch Stefan 
Published: April 2019

AbstractElectromagnetic cloaking, as challenging as it may be to the physicist and the engineer has become a topical subject over the past decade. Thanks to the transformations optics (TO) invisibility devices are in sight even though quite drastic limitations remain yet to be lifted. The extreme material properties which are deduced from TO can be achieved in practice using dispersive metamaterials. However, the bandwidth over which a metamaterial cloak is efficient is drastically limited. We design and simulate a spherical cloak which takes into account the dispersive nature of relative permittivity and permeability tensors realized by plasma-like metamaterials. This spherical cloak works over a broad frequency-band even though these materials are of a highly dispersive nature. We establish two equations of state that link the eigenvalues of the permittivity and permeability tensors in every spherical cloak regardless of the geometrical transformation. Frequency dispersive properties do not disrupt cloaking as long as the equations of states are satisfied in the metamaterial cloak.
Sea snake cathelicidin (Hc-cath) exerts a protective effect in mouse models of lung inflammation and infection
Authors: Carlile Simon R. , Shiels Jenna , Kerrigan Lauren , Delaney Rebecca , Megaw Julianne , Gilmore Brendan F. , Weldon Sinéad , Dalton John P. , Taggart Clifford C. 
Published: April 2019

AbstractWe investigated the anti-inflammatory and antibacterial activities of Hc-cath, a cathelicidin peptide derived from the venom of the sea snake, Hydrophis cyanocyntus, using in vivo models of inflammation and infection. Hc-cath function was evaluated in in vitro, in vivo in the wax moth, Galleria mellonella, and in mouse models of intraperitoneal and respiratory Pseudomonas aeruginosa infection. Hc-Cath downregulated LPS-induced pro-inflammatory responses in macrophages and significantly improved the survival of P. aeruginosa infected G. mellonella over a 5-day period. We also demonstrated, for the first time, that Hc-cath can modulate inflammation in a mouse model of LPS-induced lung inflammation by significantly reducing the release of the pro-inflammatory cytokine and neutrophil chemoattractant, KC, resulting in reduced cellular infiltration into the lungs. Moreover, Hc-cath treatment significantly reduced the bacterial load and inflammation in mouse models of P. aeruginosa intraperitoneal and respiratory infection. The effect of Hc-cath in our studies highlights the potential to develop this peptide as a candidate for therapeutic development.
Machine Learning for Diagnosis of Hematologic Diseases in Magnetic Resonance Imaging of Lumbar Spines
Authors: Hwang Eo-Jin , Jung Joon-Yong , Lee Seul Ki , Lee Sung-Eun , Jee Won-Hee 
Published: April 2019

AbstractWe aimed to assess feasibility of a support vector machine (SVM) texture classifier to discriminate pathologic infiltration patterns from the normal bone marrows in MRI. This retrospective study included 467 cases, which were split into a training (n = 360) and a test set (n = 107). A sagittal T1-weighted lumbar spinal MR image was normalized by an intervertebral disk, and bone marrows were segmented. The various kernel functions and SVM input dimensions were experimented to construct the most optimal classifier model. The accuracy and sensitivity increased as the number of training set sizes increased from 180 to 360. The test set was analyzed by SVM and two independent readers, and the accuracy and sensitivity of the SVM classifier, reader 1 and reader 2 were 82.2% and 85.5%, 79.4% and 82.3%, and 82.2% and 83.9%, respectively. The area under receiver operating characteristic curve (AUC) of the SVM classifier, reader 1 and reader 2 were 0.895, 0.879 and 0.880, respectively. The SVM texture classifier produced comparable performance to radiologists in isolating the hematologic diseases, which could support inexperienced physicians with spinal MRI to screen patients with marrow diseases, who need further diagnostic work-ups to make final decisions.
Upsurge of Enterovirus D68 and Circulation of the New Subclade D3 and Subclade B3 in Beijing, China, 2016
Authors: Shen Lingyu , Gong Cheng , Xiang Zichun , Zhang Tiegang , Li Maozhong , Li Aihua , Luo Ming , Huang Fang 
Published: April 2019

AbstractWe conducted a surveillance among acute respiratory tract infection (ARTI) cases to define the epidemiology, clinical characteristics and genetic variations of enterovirus D68 (EV-D68) in Beijing, China from 2015 to 2017. Nasopharyngeal swabs and sputum were collected from 30 sentinel hospitals in Beijing and subjected to EV and EV-D68 detection by real-time PCR. The VP1 gene region and complete genome sequences of EV-D68 positive cases were analyzed. Of 21816 ARTI cases, 619 (2.84%) were EV positive and 42 cases were EV-D68 positive. The detection rates of EV-D68 were 0 (0/6644) in 2015, 0.53% (40/7522) in 2016 and 0.03% (2/7650) in 2017, respectively. Two peaks of EV-D68 infections occurred in late summer and early-winter. Ten cases (23.81%) with upper respiratory tract infection and 32 cases (76.19%) presented with pneumonia, including 3 cases with severe pneumonia. The phylogenetic analysis suggested 15 subclade D3 strains and 27 subclade B3 strains of EV-D68 were circulated in China from 2016 to 2017. A total of 52 amino acid polymorphisms were identified between subclades D1 and D3. These data suggest an upsurge of EV-D68 occurred in Beijing in 2016, the new subclade D3 emerged in 2016 and co-circulated with subclade B3 between 2016 and 2017.
Plasmonic Schottky photodetector with metal stripe embedded into semiconductor and with a CMOS-compatible titanium nitride
Authors: Gosciniak Jacek , Atar Fatih B. , Corbett Brian , Rasras Mahmoud 
Published: April 2019

AbstractHere we propose an original waveguide-integrated plasmonic Schottky photodetector that takes full advantage of a thin metal stripe embedded entirely into a semiconductor. The photodetector is based on the long-range dielectric-loaded surface plasmon polariton waveguide with a metal stripe deposited on top of a semiconductor rib and covered by another semiconductor. As the metal stripe is entirely surrounded by semiconductor, all hot electrons with appropriate k-vectors can participate in transitions that highly enhances the electron transfer, and consequently the internal quantum efficiency. In addition, a high coupling efficiency from the photonic waveguide to the photodetector is simulated exceeding 90 % which enhances the external quantum efficiency. Calculations show that a responsivity exceeding 0.5A/Wcan be achieved at telecom wavelength of 1550nmand the bandwidth can exceed 100GHz. Furthermore, it is shown that titanium nitride is a perfect material for the photodetector as it provides a low Fermi energy and long electron mean free path that enhance the hot electron transfer to the semiconductor. In addition, it shows reasonable metallic behavior and CMOS compatibility. Measurements showed that the Schottky barrier height between titanium nitride and p-doped silicon reaches 0.69–0.70eVthat matches the optimum signal-to-noise ratio operation calculated at 0.697eV.
Stem cell models as an in vitro model for predictive toxicology
Authors: Lynch Stephen , Pridgeon Chris S. , Duckworth Carrie A. , Sharma Parveen , Park B. Kevin , Goldring Chris E.P. 
Published: April 2019

Abstract
Adverse drug reactions (ADRs) are the unintended side effects of drugs. They are categorised as either predictable or unpredictable drug-induced injury and may be exhibited after a single or prolonged exposure to one or multiple compounds. Historically, toxicology studies rely heavily on animal models to understand and characterise the toxicity of novel compounds. However, animal models are imperfect proxies for human toxicity and there have been several high-profile cases of failure of animal models to predict human toxicity e.g. fialuridine, TGN1412 which highlight the need for improved predictive models of human toxicity. As a result, stem cell-derived models are under investigation as potential models for toxicity during early stages of drug development. Stem cells retain the genotype of the individual from which they were derived, offering the opportunity to model the reproducibility of rare phenotypes in vitro. Differentiated 2D stem cell cultures have been investigated as models of hepato- and cardiotoxicity. However, insufficient maturity, particularly in the case of hepatocyte-like cells, means that their widespread use is not currently a feasible method to tackle the complex issues of off-target and often unpredictable toxicity of novel compounds. This review discusses the current state of the art for modelling clinically relevant toxicities, e.g. cardio- and hepatotoxicity, alongside the emerging need for modelling gastrointestinal toxicity and seeks to address whether stem cell technologies are a potential solution to increase the accuracy of ADR predictivity in humans.